{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T15:05:38Z","timestamp":1791990338537,"version":"4.4.0"},"reference-count":73,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T00:00:00Z","timestamp":1738800000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["WT202843\/Z\/16\/Z"],"award-info":[{"award-number":["WT202843\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM116032"],"award-info":[{"award-number":["GM116032"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/W02618X\/1"],"award-info":[{"award-number":["MR\/W02618X\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>\n                    The drivers of tissue necrosis in\n                    <jats:italic>Mycobacterium ulcerans<\/jats:italic>\n                    infection (Buruli ulcer disease) have historically been ascribed solely to the directly cytotoxic action of the diffusible exotoxin, mycolactone. However, its role in the clinically evident vascular component of disease aetiology remains poorly explained. We have now dissected mycolactone\u2019s effects on human primary vascular endothelial cells in vitro. We show that mycolactone-induced changes in endothelial morphology, adhesion, migration, and permeability are dependent on its action at the Sec61 translocon. Unbiased quantitative proteomics identified a profound effect on proteoglycans, driven by rapid loss of type II transmembrane proteins of the Golgi, including enzymes required for glycosaminoglycan (GAG) synthesis, combined with a reduction in the core proteins themselves. Loss of the glycocalyx is likely to be of particular mechanistic importance, since knockdown of galactosyltransferase II (beta-1,3-galactotransferase 6; B3GALT6), the GAG linker-building enzyme, phenocopied the permeability and phenotypic changes induced by mycolactone. Additionally, mycolactone depleted many secreted basement membrane components and microvascular basement membranes were disrupted in vivo during\n                    <jats:italic>M. ulcerans<\/jats:italic>\n                    infection in the mouse model. Remarkably, exogenous addition of laminin-511 reduced endothelial cell rounding, restored cell attachment and reversed the defective migration caused by mycolactone. Hence supplementing mycolactone-depleted extracellular matrix may be a future therapeutic avenue, to improve wound healing rates.\n                  <\/jats:p>","DOI":"10.7554\/elife.86931","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T10:48:11Z","timestamp":1684147691000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.86931","source":"Crossref","is-referenced-by-count":4,"title":["The Mycobacterium ulcerans toxin mycolactone causes destructive Sec61-dependent loss of the endothelial glycocalyx and vessel basement membrane to drive skin necrosis"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9499-889X","authenticated-orcid":true,"given":"Louise Tzung-Harn","family":"Hsieh","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ks66431","id-type":"ROR","asserted-by":"publisher"}],"name":"Discipline of Microbes, Infection & Immunity, School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey","place":["Guildford, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3753-1978","authenticated-orcid":true,"given":"Belinda S","family":"Hall","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ks66431","id-type":"ROR","asserted-by":"publisher"}],"name":"Discipline of Microbes, Infection & Immunity, School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey","place":["Guildford, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Jane","family":"Newcombe","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ks66431","id-type":"ROR","asserted-by":"publisher"}],"name":"Discipline of Microbes, Infection & Immunity, School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey","place":["Guildford, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Tom A","family":"Mendum","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ks66431","id-type":"ROR","asserted-by":"publisher"}],"name":"Discipline of Microbes, Infection & Immunity, School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey","place":["Guildford, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Sonia Santana","family":"Varela","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ks66431","id-type":"ROR","asserted-by":"publisher"}],"name":"Discipline of Microbes, Infection & Immunity, School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey","place":["Guildford, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Yagnesh","family":"Umrania","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013meh722","id-type":"ROR","asserted-by":"publisher"}],"name":"Cambridge Centre for Proteomics, University of Cambridge","place":["Cambridge, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Michael J","family":"Deery","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/013meh722","id-type":"ROR","asserted-by":"publisher"}],"name":"Cambridge Centre for Proteomics, University of Cambridge","place":["Cambridge, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Wei Q","family":"Shi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00k6tx165","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Chemistry, Ball State University","place":["Muncie, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"resources","vocabulary":"credit"}]},{"given":"Josu\u00e9","family":"Diaz-Delgado","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01f5ytq51","id-type":"ROR","asserted-by":"publisher"}],"name":"Texas A&M Veterinary Medical Diagnostic Laboratory","place":["College Station, United States"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Francisco J","family":"Salguero","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/018h10037","id-type":"ROR","asserted-by":"publisher"}],"name":"United Kingdom Health Security Agency, UKHSA-Porton Down","place":["Salisbury, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4843-8266","authenticated-orcid":true,"given":"Rachel E","family":"Simmonds","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00ks66431","id-type":"ROR","asserted-by":"publisher"}],"name":"Discipline of Microbes, Infection & Immunity, School of Biosciences, Faculty of Health and Medical Sciences, University of Surrey","place":["Guildford, United Kingdom"]}],"role":[{"role":"author","vocabulary":"crossref"},{"role":"corresponding-author","vocabulary":"crossref"},{"role":"conceptualization","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"4374","published-online":{"date-parts":[[2025,2,6]]},"reference":[{"key":"bib1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-15-293","type":"journal-article","article-title":"jvenn: an interactive Venn diagram viewer","volume":"15","author":"Bardou","year":"2014","journal-title":"BMC Bioinformatics"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.matbio.2017.04.003","type":"journal-article","article-title":"The provisional matrix: setting the stage for tissue repair outcomes","volume":"60\u201361","author":"Barker","year":"2017","journal-title":"Matrix Biology"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"2885","DOI":"10.1084\/jem.20160662","type":"journal-article","article-title":"Mycolactone subverts immunity by selectively blocking the Sec61 translocon","volume":"213","author":"Baron","year":"2016","journal-title":"The Journal of Experimental Medicine"},{"key":"bib4","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1021\/acschembio.7b00053","type":"journal-article","article-title":"The macrolide toxin mycolactone promotes bim-dependent apoptosis in buruli ulcer through inhibition of mTOR","volume":"12","author":"Bieri","year":"2017","journal-title":"ACS Chemical Biology"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"1989","DOI":"10.1161\/ATVBAHA.108.177402","type":"journal-article","article-title":"Tissue factor in coagulation: which? where? when?","volume":"29","author":"Butenas","year":"2009","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"2981","DOI":"10.7150\/ijms.60281","type":"journal-article","article-title":"Salmonella alters heparanase expression and reduces tumor metastasis","volume":"18","author":"Chiu","year":"2021","journal-title":"International Journal of Medical Sciences"},{"key":"bib7","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1111\/1523-1747.ep12500075","type":"journal-article","article-title":"Fibronectin and fibrin provide a provisional matrix for epidermal cell migration during wound reepithelialization","volume":"79","author":"Clark","year":"1982","journal-title":"The Journal of Investigative Dermatology"},{"key":"bib8","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-019-1110-9","type":"journal-article","article-title":"The clinical and mutational spectrum of B3GAT3 linkeropathy: two case reports and literature review","volume":"14","author":"Colman","year":"2019","journal-title":"Orphanet Journal of Rare Diseases"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"1185","DOI":"10.2217\/fmb.11.101","type":"journal-article","article-title":"Treating Mycobacterium ulcerans disease (Buruli ulcer): from surgery to antibiotics, is the pill mightier than the knife?","volume":"6","author":"Converse","year":"2011","journal-title":"Future Microbiology"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1002\/(sici)1097-4644(19960101)60:13.0.co;2-l","type":"journal-article","article-title":"Alterations in endothelial cell proteinase and inhibitor polarized secretion following treatment with interleukin-1, phorbol ester, and human melanoma cell conditioned medium","volume":"60","author":"Cottam","year":"1996","journal-title":"Journal of Cellular Biochemistry"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.1161\/01.RES.0000191547.64391.e3","type":"journal-article","article-title":"Endothelial extracellular matrix: biosynthesis, remodeling, and functions during vascular morphogenesis and neovessel stabilization","volume":"97","author":"Davis","year":"2005","journal-title":"Circulation Research"},{"key":"bib12","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1111\/boc.201800030","type":"journal-article","article-title":"Sec61 blockade by mycolactone: a central mechanism in Buruli ulcer disease","volume":"110","author":"Demangel","year":"2018","journal-title":"Biology of the Cell"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"183","DOI":"10.15252\/embj.201694756","type":"journal-article","article-title":"Endothelial basement membrane laminin 511 is essential for shear stress response","volume":"36","author":"Di Russo","year":"2017","journal-title":"The EMBO Journal"},{"key":"bib14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0008709","type":"journal-article","article-title":"Mycolactone induces cell death by SETD1B-dependent degradation of glutathione","volume":"14","author":"F\u00f6rster","year":"2020","journal-title":"PLOS Neglected Tropical Diseases"},{"key":"bib15","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009107","type":"journal-article","article-title":"Mycolactone toxin induces an inflammatory response by targeting the IL-1\u03b2 pathway: Mechanistic insight into Buruli ulcer pathophysiology","volume":"16","author":"Foulon","year":"2020","journal-title":"PLOS Pathogens"},{"key":"bib16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003066","type":"journal-article","article-title":"Proteomic analysis of the action of the Mycobacterium ulcerans toxin mycolactone: targeting host cells cytoskeleton and collagen","volume":"8","author":"Gama","year":"2014","journal-title":"PLOS Neglected Tropical Diseases"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"854","DOI":"10.1126\/science.283.5403.854","type":"journal-article","article-title":"Mycolactone: a polyketide toxin from Mycobacterium ulcerans required for virulence","volume":"283","author":"George","year":"1999","journal-title":"Science"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/j.molcel.2020.06.013","type":"journal-article","article-title":"Structure of the inhibited state of the sec translocon","volume":"79","author":"G\u00e9rard","year":"2020","journal-title":"Molecular Cell"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0013839","type":"journal-article","article-title":"Antioxidants protect keratinocytes against M. ulcerans mycolactone cytotoxicity","volume":"5","author":"Gr\u00f6nberg","year":"2010","journal-title":"PLOS ONE"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"E5910","DOI":"10.1073\/pnas.1705242114","type":"journal-article","article-title":"Sec61 blockade by mycolactone inhibits antigen cross-presentation independently of endosome-to-cytosol export","volume":"114","author":"Grotzke","year":"2017","journal-title":"PNAS"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"12833","DOI":"10.1073\/pnas.1016496108","type":"journal-article","article-title":"Mycolactone impairs T cell homing by suppressing microRNA control of L-selectin expression","volume":"108","author":"Guenin-Mac\u00e9","year":"2011","journal-title":"PNAS"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"1501","DOI":"10.1172\/JCI66576","type":"journal-article","article-title":"Mycolactone activation of Wiskott-Aldrich syndrome proteins underpins Buruli ulcer formation","volume":"123","author":"Guenin-Mac\u00e9","year":"2013","journal-title":"The Journal of Clinical Investigation"},{"key":"bib23","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053715","type":"journal-article","article-title":"Perlecan maintains microvessel integrity in vivo and modulates their formation in vitro","volume":"8","author":"Gustafsson","year":"2013","journal-title":"PLOS ONE"},{"key":"bib24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004061","type":"journal-article","article-title":"The pathogenic mechanism of the Mycobacterium ulcerans virulence factor, mycolactone, depends on blockade of protein translocation into the ER","volume":"10","author":"Hall","year":"2014","journal-title":"PLOS Pathogens"},{"key":"bib25","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.788146","type":"journal-article","article-title":"The one that got away: how macrophage-derived IL-1\u03b2 Escapes the mycolactone-dependent sec61 blockade in buruli ulcer","volume":"12","author":"Hall","year":"2021","journal-title":"Frontiers in Immunology"},{"key":"bib26","doi-asserted-by":"publisher","first-page":"841","DOI":"10.1080\/15548627.2021.1961067","type":"journal-article","article-title":"Inhibition of the SEC61 translocon by mycolactone induces a protective autophagic response controlled by EIF2S1-dependent translation that does not require ULK1 activity","volume":"18","author":"Hall","year":"2022","journal-title":"Autophagy"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"131","DOI":"10.3233\/BIR-180205","type":"journal-article","article-title":"Endothelial barrier reinforcement relies on flow-regulated glycocalyx, a potential therapeutic target","volume":"56","author":"Harding","year":"2019","journal-title":"Biorheology"},{"key":"bib28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1010280","type":"journal-article","article-title":"Aberrant stromal tissue factor localisation and mycolactone-driven vascular dysfunction, exacerbated by IL-1\u03b2, are linked to fibrin formation in Buruli ulcer lesions","volume":"18","author":"Hsieh","year":"2022","journal-title":"PLOS Pathogens"},{"key":"bib29","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1089\/wound.2014.0533","type":"journal-article","article-title":"Laminins: roles and utility in wound repair","volume":"4","author":"Iorio","year":"2015","journal-title":"Advances in Wound Care"},{"key":"bib30","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-04525-w","type":"journal-article","article-title":"Laminin heparin-binding peptides bind to several growth factors and enhance diabetic wound healing","volume":"9","author":"Ishihara","year":"2018","journal-title":"Nature Communications"},{"key":"bib31","doi-asserted-by":"publisher","first-page":"1708","DOI":"10.1080\/09168451.2018.1484272","type":"journal-article","article-title":"Signal-anchor sequences are an essential factor for the Golgi-plasma membrane localization of type II membrane proteins","volume":"82","author":"Kikegawa","year":"2018","journal-title":"Bioscience, Biotechnology, and Biochemistry"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"1884","DOI":"10.1177\/15353702211015628","type":"journal-article","article-title":"Natural antioxidants attenuate mycolactone toxicity to RAW 264.7 macrophages","volume":"246","author":"Kwaffo","year":"2021","journal-title":"Experimental Biology and Medicine"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"935","DOI":"10.1016\/j.ajhg.2013.04.016","type":"journal-article","article-title":"Defective initiation of glycosaminoglycan synthesis due to B3GALT6 mutations causes a pleiotropic Ehlers-Danlos-syndrome-like connective tissue disorder","volume":"92","author":"Malfait","year":"2013","journal-title":"American Journal of Human Genetics"},{"key":"bib34","doi-asserted-by":"publisher","first-page":"1404","DOI":"10.1242\/jcs.182352","type":"journal-article","article-title":"Mechanistic insights into the inhibition of Sec61-dependent co- and post-translational translocation by mycolactone","volume":"129","author":"McKenna","year":"2016","journal-title":"Journal of Cell Science"},{"key":"bib35","doi-asserted-by":"publisher","first-page":"1307","DOI":"10.1242\/jcs.198655","type":"journal-article","article-title":"Mycolactone reveals the substrate-driven complexity of Sec61-dependent transmembrane protein biogenesis","volume":"130","author":"McKenna","year":"2017","journal-title":"Journal of Cell Science"},{"key":"bib36","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1038\/s41431-019-0464-8","type":"journal-article","article-title":"Expansion of B4GALT7 linkeropathy phenotype to include perinatal lethal skeletal dysplasia","volume":"27","author":"Mihalic Mosher","year":"2019","journal-title":"European Journal of Human Genetics"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"1713","DOI":"10.1083\/jcb.143.6.1713","type":"journal-article","article-title":"Roles for laminin in embryogenesis: exencephaly, syndactyly, and placentopathy in mice lacking the laminin alpha5 chain","volume":"143","author":"Miner","year":"1998","journal-title":"The Journal of Cell Biology"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"1750","DOI":"10.1074\/mcp.RA118.000824","type":"journal-article","article-title":"Proteomics reveals scope of mycolactone-mediated sec61 blockade and distinctive stress signature","volume":"17","author":"Morel","year":"2018","journal-title":"Molecular & Cellular Proteomics"},{"key":"bib39","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06188-z","type":"journal-article","article-title":"Proteomics reveals signal peptide features determining the client specificity in human TRAP-dependent ER protein import","volume":"9","author":"Nguyen","year":"2018","journal-title":"Nature Communications"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1002\/jcp.1041540325","type":"journal-article","article-title":"Fibronectin promotes the elongation of microvessels during angiogenesis in vitro","volume":"154","author":"Nicosia","year":"1993","journal-title":"Journal of Cellular Physiology"},{"key":"bib41","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005011","type":"journal-article","article-title":"Mycolactone-dependent depletion of endothelial cell thrombomodulin is strongly associated with fibrin deposition in buruli ulcer lesions","volume":"11","author":"Ogbechi","year":"2015","journal-title":"PLOS Pathogens"},{"key":"bib42","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0427-y","type":"journal-article","article-title":"Inhibition of Sec61-dependent translocation by mycolactone uncouples the integrated stress response from ER stress, driving cytotoxicity via translational activation of ATF4","volume":"9","author":"Ogbechi","year":"2018","journal-title":"Cell Death & Disease"},{"key":"bib43","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02363-z","type":"journal-article","article-title":"An alternative pathway for membrane protein biogenesis at the endoplasmic reticulum","volume":"4","author":"O\u2019Keefe","year":"2021","journal-title":"Commun Biol"},{"key":"bib44","doi-asserted-by":"publisher","first-page":"6835","DOI":"10.1111\/febs.15905","type":"journal-article","article-title":"Membrane protein biogenesis at the ER: the highways and byways","volume":"289","author":"O\u2019Keefe","year":"2022","journal-title":"The FEBS Journal"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1161\/01.atv.11.6.1752","type":"journal-article","article-title":"Metabolism and turnover of cell surface-associated heparan sulfate proteoglycan and chondroitin sulfate proteoglycan in normal and cholesterol-enriched macrophages","volume":"11","author":"Owens","year":"1991","journal-title":"Arteriosclerosis and Thrombosis"},{"key":"bib46","doi-asserted-by":"publisher","DOI":"10.3390\/ijms222112007","type":"journal-article","article-title":"Inhibitors of the Sec61 complex and novel high throughput screening strategies to target the protein translocation pathway","volume":"22","author":"Pauwels","year":"2021","journal-title":"International Journal of Molecular Sciences"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"D543","DOI":"10.1093\/nar\/gkab1038","type":"journal-article","article-title":"The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences","volume":"50","author":"Perez-Riverol","year":"2022","journal-title":"Nucleic Acids Research"},{"key":"bib48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005738","type":"journal-article","article-title":"Dengue Virus NS1 disrupts the endothelial glycocalyx, leading to hyperpermeability","volume":"12","author":"Puerta-Guardo","year":"2016","journal-title":"PLOS Pathogens"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1007\/s00424-007-0212-8","type":"journal-article","article-title":"The endothelial glycocalyx: composition, functions, and visualization","volume":"454","author":"Reitsma","year":"2007","journal-title":"Pflugers Archiv"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1111\/cmi.12547","type":"journal-article","article-title":"Recent advances: role of mycolactone in the pathogenesis and monitoring of Mycobacterium ulcerans infection\/Buruli ulcer disease","volume":"18","author":"Sarfo","year":"2016","journal-title":"Cellular Microbiology"},{"key":"bib51","doi-asserted-by":"publisher","first-page":"4612","DOI":"10.1111\/febs.15274","type":"journal-article","article-title":"Identification of signal peptide features for substrate specificity in human Sec62\/Sec63-dependent ER protein import","volume":"287","author":"Schorr","year":"2020","journal-title":"The FEBS Journal"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"2194","DOI":"10.4049\/jimmunol.0802294","type":"journal-article","article-title":"Mycolactone inhibits monocyte cytokine production by a posttranscriptional mechanism","volume":"182","author":"Simmonds","year":"2009","journal-title":"Journal of Immunology"},{"key":"bib53","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1083\/jcb.153.5.933","type":"journal-article","article-title":"Endothelial cell laminin isoforms, laminins 8 and 10, play decisive roles in T cell recruitment across the blood-brain barrier in experimental autoimmune encephalomyelitis","volume":"153","author":"Sixt","year":"2001","journal-title":"The Journal of Cell Biology"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/s41586-022-05336-2","type":"journal-article","article-title":"Mechanism of an intramembrane chaperone for multipass membrane proteins","volume":"611","author":"Smalinskait\u0117","year":"2022","journal-title":"Nature"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"647","DOI":"10.1021\/ol0172828","type":"journal-article","article-title":"Total synthesis of the mycolactones","volume":"4","author":"Song","year":"2002","journal-title":"Organic Letters"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"1256","DOI":"10.1016\/j.celrep.2016.12.092","type":"journal-article","article-title":"Endothelial basement membrane laminin 511 contributes to endothelial junctional tightness and thereby inhibits leukocyte transmigration","volume":"18","author":"Song","year":"2017","journal-title":"Cell Reports"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"90","DOI":"10.4161\/cam.22236","type":"journal-article","article-title":"Laminin \u03b15 guides tissue patterning and organogenesis","volume":"7","author":"Spenl\u00e9","year":"2013","journal-title":"Cell Adhesion & Migration"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/s41586-022-05330-8","type":"journal-article","article-title":"Substrate-driven assembly of a translocon for multipass membrane proteins","volume":"611","author":"Sundaram","year":"2022","journal-title":"Nature"},{"key":"bib59","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.675747","type":"journal-article","article-title":"Helicobacter pylori-induced heparanase promotes H. pylori colonization and gastritis","volume":"12","author":"Tang","year":"2021","journal-title":"Frontiers in Immunology"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1128\/MCB.22.4.1194-1202.2002","type":"journal-article","article-title":"Deletion of the laminin alpha4 chain leads to impaired microvessel maturation","volume":"22","author":"Thyboll","year":"2002","journal-title":"Molecular and Cellular Biology"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1126\/science.aad4992","type":"journal-article","article-title":"Structure of the Sec61 channel opened by a signal sequence","volume":"351","author":"Voorhees","year":"2016","journal-title":"Science"},{"key":"bib62","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1016\/j.bbamem.2007.09.003","type":"journal-article","article-title":"Endothelial adherens and tight junctions in vascular homeostasis, inflammation and angiogenesis","volume":"1778","author":"Wallez","year":"2008","journal-title":"Biochimica et Biophysica Acta"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1016\/j.atherosclerosis.2019.04.210","type":"journal-article","article-title":"Understanding mechanobiology in cultured endothelium: A review of the orbital shaker method","volume":"285","author":"Warboys","year":"2019","journal-title":"Atherosclerosis"},{"key":"bib64","doi-asserted-by":"crossref","first-page":"10260","DOI":"10.1016\/S0021-9258(18)90959-2","type":"journal-article","article-title":"Proteoglycans synthesized by rat ovarian granulosa cells in culture: isolation, fractionation, and characterization of proteoglycans associated with the cell layer","volume":"259","author":"Yanagishita","year":"1984","journal-title":"The Journal of Biological Chemistry"},{"key":"bib65","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1093\/ckj\/sfz042","type":"journal-article","article-title":"The role of endothelial glycocalyx in health and disease","volume":"12","author":"Yilmaz","year":"2019","journal-title":"Clinical Kidney Journal"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1007\/s40475-018-0166-2","type":"journal-article","article-title":"Buruli Ulcer: a review of the current knowledge","volume":"5","author":"Yotsu","year":"2018","journal-title":"Current Tropical Medicine Reports"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"101","DOI":"10.4161\/cam.22680","type":"journal-article","article-title":"Laminin isoforms in endothelial and perivascular basement membranes","volume":"7","author":"Yousif","year":"2013","journal-title":"Cell Adhesion & Migration"},{"key":"bib68","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043168","type":"journal-article","article-title":"The structural stability of the endothelial glycocalyx after enzymatic removal of glycosaminoglycans","volume":"7","author":"Zeng","year":"2012","journal-title":"PLOS ONE"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"6816","DOI":"10.1073\/pnas.1804262115","type":"journal-article","article-title":"Potent laminin-inspired antioxidant regenerative dressing accelerates wound healing in diabetes","volume":"115","author":"Zhu","year":"2018","journal-title":"PNAS"},{"key":"bib70","doi-asserted-by":"publisher","first-page":"9279","DOI":"10.1021\/acs.joc.5b01765","type":"journal-article","article-title":"Total synthesis and biological evaluation of ipomoeassin F and its unnatural 11R-Epimer","volume":"80","author":"Zong","year":"2015","journal-title":"The Journal of Organic Chemistry"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"8450","DOI":"10.1021\/jacs.8b13506","type":"journal-article","article-title":"Ipomoeassin F Binds Sec61\u03b1 to inhibit protein translocation","volume":"141","author":"Zong","year":"2019","journal-title":"Journal of the American Chemical Society"},{"key":"bib72","doi-asserted-by":"publisher","first-page":"16226","DOI":"10.1021\/acs.joc.0c01659","type":"journal-article","article-title":"Ring expansion leads to a more potent analogue of ipomoeassin F","volume":"85","author":"Zong","year":"2020","journal-title":"The Journal of Organic Chemistry"},{"key":"dataset1","type":"dataset","article-title":"Mycolactone causes destructive Sec61-dependent loss of the endothelial glycocalyx and basement membrane: a new indirect mechanism driving tissue necrosis in Mycobacterium ulcerans infection","volume-title":"PRIDE","author":"Hall","year":"2025","unstructured":"Hall BS, Umrania Y, Deery MJ, Simmonds RE. 2025. Mycolactone causes destructive Sec61-dependent loss of the endothelial glycocalyx and basement membrane: a new indirect mechanism driving tissue necrosis in Mycobacterium ulcerans infection. PRIDE. http:\/\/www.ebi.ac.uk\/pride\/archive\/projects\/PXD037489. PXD037489."}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/86931\/elife-86931-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/86931\/elife-86931-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/86931","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T09:53:36Z","timestamp":1787565216000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/86931"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,6]]},"references-count":73,"alternative-id":["10.7554\/eLife.86931"],"URL":"https:\/\/doi.org\/10.7554\/elife.86931","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.02.21.529382","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2023.02.21.529382","asserted-by":"object"}],"is-same-as":[{"id-type":"doi","id":"10.7554\/eLife.86931.3","asserted-by":"subject"}],"is-version-of":[{"id-type":"doi","id":"10.7554\/eLife.86931.1","asserted-by":"subject"},{"id-type":"doi","id":"10.7554\/eLife.86931.2","asserted-by":"subject"}],"is-supplemented-by":[{"id-type":"accession","id":"PXD037489","asserted-by":"subject"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,6]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"RP86931"}}